Monoclonal Gammopathy of Undetermined Significance and Risk of Infections: A Population-Based Study

Abstract Abstract 4053 Background: Based on clinical case reports and small hospital-based patient series, monoclonal gammopathy of undetermined significance (MGUS) has been reported to increase morbidity due to bacterial infections; however, no comprehensive evaluation has been conducted. Patients and methods: Using population-based data from Sweden, we assessed the risks of viral and bacterial infections (reported to the Patient-Registry) in 5,326 MGUS patients diagnosed 1958–2006, compared to 20,161 matched population-based controls. We fit Cox proportional hazard models to estimate hazard ratios (HRs) as measures of risk. Results: At 5 years of follow-up MGUS patients had a 2.1-fold (95% confidence interval (CI) 2.1–2.3) increased risk of developing any infection compared to controls; at 10 years of follow-up, the risk was very similar (HR=2.2; 95% CI 2.0–2.3). MGUS patients had a 2.2-fold (95% CI 2.0–2.4) and 2.1-fold (95% CI 2.0–2.3) increased risk of developing bacterial infections at 5 and 10 years, respectively. A significantly increased risk (P<0.05) was found for pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis and meningitis. We also assessed the risk of developing viral infections; compared to controls, MGUS patients had a 2.7-fold (95% CI 2.2–3.3) and 2.9-fold (95% CI 2.3–3.7) increased risk at 5 and 10 years, respectively, with a significantly increased risk for influenza and herpes infections (P<0.05). Risk of infections did not differ by MGUS isotype. MGUS patients with an M-protein >2.5 g/dL at diagnosis had higher risks of infections compared to those <0.5 g/dL. However, compared to controls the risk of infections was also significantly increased among MGUS patients with a concentration <0.5 g/dL. MGUS patients with (versus without) infections had no excess risk of developing multiple myeloma or related malignancies. Summary and Conclusions: Based on over 5,000 MGUS patients, we found a 2-fold higher risk of developing bacterial and viral infections, compared to controls. The risk was highest among MGUS patients with high M-protein concentrations at diagnosis (>2.5 g/dL); however, the risk was still significantly increased among those with a concentration <0.5 g/dL. Infections in patients with MGUS were not associated with an increased risk of malignant transformation. We recently showed that patients with MGUS have a 3-fold risk of death in bacterial infections. Our findings may have clinical implications for treatment strategies and prophylactic measures, as well as surveillance of MGUS patients. Disclosures: No relevant conflicts of interest to declare.

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Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study

Blood ◽

10.1182/blood-2010-04-282848 ◽

2010 ◽

Vol 116 (15) ◽

pp. 2651-2655 ◽

Cited By ~ 62

Author(s):

Sigurdur Y. Kristinsson ◽

Min Tang ◽

Ruth M. Pfeiffer ◽

Magnus Björkholm ◽

Cecilie Blimark ◽

...

Keyword(s):

Bone Disease ◽

Monoclonal Gammopathy ◽

Protein Concentration ◽

Population Based ◽

M Protein ◽

Multiple Fractures ◽

Population Based Study ◽

Increased Risk ◽

Undetermined Significance

AbstractPatients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.

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Multiple Myeloma and Infections: A Population-Based Study Based On 9,610 Multiple Myeloma Patients

Blood ◽

10.1182/blood.v120.21.945.945 ◽

2012 ◽

Vol 120 (21) ◽

pp. 945-945

Author(s):

Cecilie Blimark ◽

Ulf-Henrik Mellqvist ◽

Ola Landgren ◽

Magnus Björkholm ◽

Malin L Hultcrantz ◽

...

Keyword(s):

Multiple Myeloma ◽

Bacterial Infections ◽

Viral Infections ◽

Normal Population ◽

Large Population ◽

Population Based ◽

First Year ◽

Population Based Study ◽

Prophylactic Measures ◽

Increased Risk

Abstract Abstract 945 Background Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM). No large population-based evaluation has been made to assess the risk of infections in MM patients compared to the normal population. Therefore, we performed a large study, using population-based data from Sweden, to estimate the risk of bacterial and viral infections among 9,610 MM patients compared to 37,718 matched controls. Methods We gathered information on all MM patients reported to the nationwide Swedish Cancer Registry from 1988 to 2004, with follow-up to 2007. For each MM patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on occurrence and date of infections was obtained from the centralized Swedish Patient registry that captures information on individual patient-based discharge diagnosis from inpatient (with very high coverage) and outpatient care (since 2000). Cox proportional hazard models were used to estimate the overall, one- and five-year risk of infections. In addition, the effect of gender, age and calendar period of diagnosis was evaluated. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for the occurrence of different infections. Results Overall, MM patients had a 6-fold (HR= 5.9; 95% CI=5.7-6.1) risk of developing any infection compared to matched controls (Figure). The increased risk of developing a bacterial infection was 6-fold (HR=5.9; 95%; CI=5.6-6.1), and for viral infections 9-fold (HR=9.0; 95% CI=8.0-10.1), compared to controls. More specifically, MM patients had an increased risk (p<0.05) of the following bacterial infections: cellulitis (HR=2.6; 95% CI =2.2-3.1), osteomyelitis (HR=3.0; 95% CI 2.0–4.4), endocarditis (HR=4.4; 95% CI 2.9–6.6), meningitis (HR=14.5; 95% CI 9.1–23.0), pneumonia (HR=6.2; 95% CI 5.9–6.5), pyelonephritis (HR=2.5; 95% CI 2.1–3.0), and septicaemia (HR=13.7; 95% CI 12.5–14.9) and for the viral infections influenza (HR=5.4; 95% CI 4.4–6.7) and herpes zoster (HR=12.8; 95% CI 10.5–15.5). The risk of infections was highest during the first year after diagnosis; the risk of bacterial infections was 11-fold (95% CI 10.7–12.9) and the risk of viral infections was 18-fold (95% CI 13.5–24.4) higher compared to controls during the first year after diagnosis. MM patients diagnosed in the more recent calendar periods had significantly higher risk of infections, reflected in a 1.6-fold (95% CI=1.5-1.7) and 2-fold (95% CI=1.9-2.1) increased risk in patients diagnosed during 1994–1999 and 2000–2004, compared to patients diagnosed 1986–1993. Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 9,000 MM patients and 35,000 matched controls, we found that bacterial and viral infections represent a major threat to myeloma patients. We found the risk of specific infections like pneumonia, and septicemia to be over ten times higher in patients than in controls during the first year after MM diagnosis. Importantly, the risk of infections increased in more recent years. The effect on infectious complications due to novel drugs in the treatment of MM needs to be established and trials on prophylactic measures are required. Disclosures: Mellqvist: Janssen, Celgene: Honoraria.

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Development Of Solid Malignancies In Patients With Monoclonal Gammopathy Of Undetermined Significance (MGUS): A Population-Based Study Of 17,315 Patients

Blood ◽

10.1182/blood.v122.21.3134.3134 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3134-3134

Author(s):

Lindsey E. Roeker ◽

Dirk Larson ◽

Robert Kyle ◽

Shaji K Kumar ◽

Angela Dispenzieri ◽

...

Keyword(s):

Solid Tumor ◽

Monoclonal Gammopathy ◽

Research Funding ◽

Population Based ◽

Solid Malignancy ◽

Solid Malignancies ◽

Increased Risk ◽

Diagnosis Date ◽

Undetermined Significance

Abstract Background While patients with monoclonal gammopathy of undetermined significance (MGUS) are known to be at an increased risk of developing multiple myeloma, Waldenström macroglobulinemia, and primary amyloidosis, the risk of developing non-hematologic malignancies is less clear. A recent report suggested that MGUS patients have a 1.56-fold increased risk of developing nonhematologic malignancies. An excess risk of developing nonmelanoma skin (RR = 2.04), endocrine (RR = 3.34), breast (RR = 1.32), kidney and urinary tract (1.58), respiratory (RR = 1.42), male reproductive system (RR = 1.32), and GI cancers (RR = 1.25) has been reported for people with MGUS (Blood Oct 13 2011;118(15):4086-4092). This study constructed a cohort by discovering MGUS status through medical workup. Therefore, associations discovered might be related to the reason the test was performed more than the result of the test. This study aimed to determine if there was an increased risk of solid malignancies in persons with MGUS using a large, population-based, systematically screened cohort. Methods The population-based cohort established to estimate the prevalence of MGUS was examined for this study (N Engl J Med 2006; 354:1362-1369). Of the 28,038 residents of Olmsted County, Minnesota age 50 years or older as of January 1, 1995, 21,463 individuals' serum samples were collected. All samples were evaluated with serum electrophoresis and immunofixation to determine MGUS status. The Mayo Clinic Medical Index from 1/1/1975 to last follow up or 5/31/2006 was used to link MGUS status to other diagnoses. All patients diagnosed with a solid malignancy were identified, and disease prevalence was determined for cases and controls. For MGUS patients who progressed to MM or related disorder, only solid malignancy diagnoses made prior to progression was considered. A second analysis was performed in which only malignancies that developed after the MGUS screening or diagnosis date were considered. Results 17,315 patients with 435,021 person-years of follow-up were included in the study. Any patient who was blinded in the initial cohort could not be included. Patients with MGUS (n=605) had a mean follow up of 24.64 years (range 0.11 to 30.57) while controls (n=16,710) had a mean of 25.14 years (range 0.01 to 31.40) of follow up. The risk ratio for developing any solid tumor was 1.08 (95% CI 0.94 to 1.25). Persons with MGUS had a 1.61-fold increased risk of developing respiratory tumors over controls. MGUS patients did not have a significantly increased risk of developing cancer in any other anatomical position studied, including bone, brain, breast, endocrine, eye, gastrointestinal, kidney, skin (melanoma or non-melanoma), oral/nasal/pharyngeal, reproductive, or salivary gland. MGUS patients were not found to be at increased risk of developing tumors with a specific pathology over controls. The second analysis, which considered only tumors that developed after the MGUS screening or diagnosis date, showed that MGUS patients were not at an increased risk of respiratory tumors (RR 1.28, p=0.21). According to this analysis, MGUS patients are at decreased risk of developing non-melanoma skin cancer (RR 0.76, p=0.003). No statistically significant increased risk of any solid tumor was identified through this analysis. Conclusion This study used a systematically screened population-based cohort to determine if patients with MGUS are at an increased risk of developing solid tumors. The analysis suggests that patients with MGUS have a significantly increased risk of developing respiratory malignancies (RR 1.61, p=0.01). However, when only tumors diagnosed after MGUS screening or diagnosis date were considered, this risk was no longer significant (RR 1.28, p=0.21). Contrary to previous reports, we did not find patients with MGUS to be at an increased risk of developing other solid malignancies. The discrepancy between these findings and previously reported increased risk may be related to the elimination of ascertainment bias in this population-based cohort universally screened for the presence or absence of MGUS. Accurately understanding the risks associated with MGUS, a condition affecting 3% percent of the population over 50 years of age, may allow for more informed recommendations for screening and counseling for these patients. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding.

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Five years’ Follow-Up Study For Frequency Of Monoclonal Gammopathy Of Undetermined Significance (MGUS) In a Korean Elderly Urban Cohort

Blood ◽

10.1182/blood.v122.21.5332.5332 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5332-5332

Author(s):

Yun-Gyoo Lee ◽

Soo-Mee Bang ◽

Jeong-Ok Lee ◽

Song Jung Han ◽

Kim Ki Woong ◽

...

Keyword(s):

Multiple Myeloma ◽

Monoclonal Gammopathy ◽

M Protein ◽

Risk Of Death ◽

Follow Up Study ◽

Significant Difference ◽

Korean Elderly ◽

Second Wave ◽

Undetermined Significance

Abstract Background The prevalence of monoclonal gammopathy of undetermined significance (MGUS) increases with patient age and varies by race. However, reliable data on the epidemiology of MGUS is limited in Korea. We previously reported the prevalence of MGUS among 1000 participants of a Korean Elderly Urban Cohort recruited from 2005 to 2006 (First Wave, Park HK Am J Hematol. 2011;86:752-5); age and gender-adjusted prevalence of MGUS was estimated as 3.3% (95% confidence interval [CI] = 2.0-4.6%). Here, we report the five years’ follow-up study for frequency of MGUS between 2010 and 2011. Methods Korean Longitudinal Study on Health and Aging (KLoSHA) is a population-based, prospective cohort study of health, aging, and common geriatric diseases in a population aged ≥ 65 years in Seongnam-si, a satellite city of Seoul. Of the random sample of 1118 candidates from 61,730 Korean elderly individuals, 698 respondents agreed to participate in baseline KLoSHA study between 2005 and 2006. A total of 680 with available samples were screened for MGUS. We followed them and collected their serum between 2010 and 2011 (Second Wave). The screening of MGUS in the Second Wave was performed using serum protein electrophoresis followed by immunofixation assays; MGUS was defined by the presence of a serum monoclonal protein (M-protein), at a concentration <3 g/dL, and in the absence of end organ damage. Bone marrow study was not performed unless the patient was suspicious of multiple myeloma. To validate complete follow-up data, information regarding vital status was obtained from the National Population Registry of Korea National Statistical Office by using a unique resident registration number. Overall survival was calculated from the date of First wave to death from any cause. Results Of the 680 respondents (21 with MGUS, 659 without MGUS) in the First Wave, 361 (53%) agreed to participate in the Second Wave. Causes of nonattendance were death in 20%, refusal in 19%, move to other area in 6%, and loss to contact in 3%. Of the 361 respondents, 10 were identified to have MGUS. Overall frequency of MGUS is 2.8% (95% CI: 1.3 - 5.0%). Among 21 patients with MGUS in the First Wave, 9 were followed up in the Second Wave. Six of them showed persistent MGUS. One of them showed mild anemia with persistent M-protein of 1.4g/dL suggestive of progression to multiple myeloma, but was not confirmed because of early death just after screening. Interestingly, M-protein was disappeared in remaining 2 patients with MGUS in the First wave. Among 659 respondents without MGUS in the First Wave, 352 were followed up in the Second Wave. Four of them were newly diagnosed with MGUS. In Kaplan-Meier survival analysis, there was no significant difference of survival between respondents with MGUS and without MGUS in the First Wave (P = 0.66 by Log-rank test). Conclusion Five years’ follow-up data showed the natural clinical course of MGUS. The diagnosis of MGUS was not associated with an increased risk of death in Korean elderly population. The interesting finding was that M-protein was disappeared in some patients with MGUS. High rate of non-attendance (47%) in Second Wave is the major limitation. Disclosures: No relevant conflicts of interest to declare.

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No Risk of Arterial or Venous Thrombosis in Monoclonal Gammopathy of Undetermined Significance: Results from a Population-Based Study

Blood ◽

10.1182/blood.v126.23.4252.4252 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4252-4252 ◽

Cited By ~ 2

Author(s):

Ebba K Lindqvist ◽

Sigrún H. Lund ◽

Rene Costello ◽

Debra Burton ◽

Neha S Korde ◽

...

Keyword(s):

Family History ◽

Venous Thrombosis ◽

Light Chain ◽

Arterial Thrombosis ◽

Monoclonal Gammopathy ◽

Population Based ◽

Increased Risk ◽

History Of ◽

Undetermined Significance

Abstract Background Monoclonal gammopathy of undetermined significance (MGUS) is a precursor condition to multiple myeloma (MM) and other lymphoproliferative disorders. Patients with MM have an increased risk of venous and arterial thrombosis. Results from previous studies have also shown an increased risk of thrombosis in MGUS. However, these studies have been performed on clinically established cohorts, and no previous study has examined the risk of thrombosis in light chain MGUS (LC-MGUS). Methods We performed a population-based study on the longitudinal cohort of the AGES-Reykjavik Study, consisting of 5,764 elderly Icelandic men and women. Through screening all participants with free light chain analysis and serum protein electrophoresis, MGUS and LC-MGUS were identified in 299 and 52 individuals, respectively. The outcome was first incidence/occurrence of venous or arterial thrombosis, as diagnosis or as cause of death. Information on outcomes was supplemented by health care records, available from nine years prior to study baseline and for a median follow-up time of 8.8 years. Through logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate history of arterial and venous thrombosis, respectively, at study baseline. A Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% CIs for the risk of first incidence of thrombosis during follow-up. Results A history of any thrombosis during the nine years prior to diagnosis was present in 30 (10.0%) of individuals with MGUS, 13 (25.0%) of individuals with LC-MGUS, and 643 (12.0%) of individuals without MGUS. In a model adjusting for age, sex, smoking, serum cholesterol levels, diabetes, hypertension, and family history of thrombosis, the odds of having had a thrombosis was not significantly different for neither MGUS (OR = 0.75, 95% CI 0.50-1.12) nor LC-MGUS (OR = 1.81, 0.92-3.58), compared to those without MGUS. During a median follow-up time of 8.8 years, 80 (26.8%) of individuals with MGUS, 14 (26.9%) of individuals with LC-MGUS, and 1,344 (25.0%) of individuals without MGUS were diagnosed with thrombosis. Individuals with MGUS and with LC-MGUS had no increased risk of arterial thrombosis, when adjusted for age, sex, cholesterol, diabetes, hypertension, smoking, and family history of thrombosis (HR 1.04, 0.82-1.32). Similarly, no increased risk was found in MGUS or LC-MGUS for venous thrombosis, in a model adjusted for age, sex, body mass index, and previous or current cancer (HR 0.89, 0.41-1.89). Excluding individuals with a diagnosis of thrombosis occurring before baseline, or adjusting for a personal history of thrombosis, did not affect the results. Summary and conclusions In this large, population-based, screening cohort study, we found no increased risk of arterial or venous thrombosis in MGUS. A history of thrombosis was more common in individuals with LC-MGUS, which might be an effect of higher age in LC-MGUS individuals. To our knowledge, this is the first study to investigate risk of thrombosis in LC-MGUS. The results from our screened study contradict previous findings from clinically established cohorts. Future work is needed to better understand observed differences between studies and across populations. For example, potential underlying factors may include aggregation of underlying comorbidities in clinically diagnosed MGUS patients, and biological variations (shared germline genetic susceptibility) by ethnic groups. Table. Risk of thrombosis in individuals with MGUS and LC-MGUS, compared to individuals without MGUS. MGUS LC-MGUS No MGUS No. HR (95% CI) No. HR (95% CI) No. HR (95% CI) Any thrombosis* 80 (26.76%) 1.01 (0.80-1.26) 14 (26.92%) 1.13 (0.80-1.26) 1,344 (25.02%) 1.00 (Reference) Arterial thrombosis† 76 (25.42%) 1.04 (0.82-1.32) 14 (26.92%) 1.16 (0.67-2.01) 1,240 (23.08%) 1.00 (Reference) Venous thrombosis†† 7 (2.34%) 0.89 (0.41-1.89) 0 (0.0%) - 151 (2.81%) 1.00 (Reference) *Results adjusted for age and sex. † Results adjusted for age, sex, smoking, hypertension, cholesterol, diabetes, and family history of arterial thrombosis. †† Results adjusted for age, sex, body mass index, and previous or current cancer. MGUS: monoclonal gammopathy of undetermined significance, LC-MGUS: light-chain monoclonal gammopathy of undetermined significance. HR: hazard ratio, CI: confidence interval. Disclosures Landgren: Celgene: Consultancy; BMJ Publishing: Consultancy; Onyx: Research Funding; International Myeloma Foundation: Research Funding; Bristol-Myers Squibb: Consultancy; Onyx: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Medscape: Honoraria; BMJ Publishing: Honoraria; Onyx: Consultancy; Medscape: Consultancy.

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Patterns of Infectious Morbidity in Patients with Waldenström’s Macroglobulinaemia/Lymphoplasmacytic Lymphoma: A Population-Based Study

Blood ◽

10.1182/blood.v124.21.3350.3350 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3350-3350

Author(s):

Sigrun Helga Lund ◽

Malin Hultcrantz ◽

Lynn Goldin ◽

Ola Landgren ◽

Magnus Björkholm ◽

...

Keyword(s):

Bacterial Infections ◽

Viral Infections ◽

Large Population ◽

Population Based ◽

Calendar Period ◽

Lymphoplasmacytic Lymphoma ◽

Population Based Study ◽

Infectious Morbidity ◽

Prophylactic Measures ◽

Increased Risk

Abstract Background Infections are a major cause of morbidity and mortality in patients with hematologic malignancies. However, largely due to the rarity of Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), the literature on infectious morbidity is limited. Using population-based data from Sweden, we estimated the risk of bacterial and viral infections among 2,608 LPL/WM patients compared to 10,433 matched controls. Patients and Methods We identified all WM/LPL patients diagnosed 1980-2005 in the nationwide Swedish Cancer and Patient Registries, as well as a national network database including all major hematology/oncology centers; duplicate records were removed. Follow-up time was up to 2006. For each WM/LPL patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on type of infection and date of infection was obtained from the Patient Registry which captures information on all individual patient-based discharge diagnosis from inpatient (since 1964) and outpatient care (since 2000). Through linkage to the nationwide Cause of Death Registry, we identified dates of death for WM/LPL patients and controls. Cox proportional hazard models were used to estimate the overall risk of infections. Models were adjusted for sex, age, and calendar period. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for individual infections. Results Overall, WM/LPL patients had a 3.4-fold (95% CI=3.1-3.6) elevated risk of developing any infection than controls (Figure). Compared to controls, the risk of developing bacterial and viral infections was 3.2-fold (95%; CI=2.9-3.5) and 6.0-fold (95% CI=4.9-7.3) higher, respectively. More specifically, WM/LPL patients had an increased risk (p<0.05) of the following types of bacterial infections: septicaemia (HR=9.3; 95% CI 3.7-23.5), endocarditis (HR=5.0; 95% CI 2.5-10.0), pneumonia (HR=3.8; 95% CI 3.4-4.2), meningitis (HR=3.4; 95% CI 1.1-10.3), cellulitis (HR=2.6; 95% CI 2.0-3.4), osteomyelitis (HR=1.9; 95% CI 1.01-3.6), and pyelonephritis (HR=1.6; 95% CI 1.2-2.4). Regarding viral infections, WM/LPL patients had an increased risk of herpes zoster (HR=9.2; 95% CI 6.7-12.6) and influenza (HR=2.3; 95% CI 1.5-3.5). The risk of infections was highest during the first year after diagnosis. Interestingly, WM/LPL patients diagnosed in the more recent calendar periods had significantly higher risk of infections (Figure). Compared to WM/LPL patients diagnosed in 1980-1989, patients diagnosed in 1990-1999 and 2000-2004 had a 1.5-fold (95% CI=1.3-1.6) and 1.8-fold (95% CI=1.6-2.1) increased risk of any infection, respectively. The same patterns were observed when bacterial infections were analyzed separately. In analysis focusing on viral infections; there was only a significant increased risk during the most recent calendar period (p=0.027). Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 2,600 WM/LPL patients and 10,000 matched controls, we found that bacterial and viral infections represent a major threat to WM/LPL patients. This was particularly true during the first years following diagnosis. Importantly, the risk of infections increased in more recent years. The effects on infectious complications due to novel drugs in the treatment of WM/LPL need to be better defined and trials on prophylactic measures are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

Blood Cancer Journal ◽

10.1038/s41408-021-00480-w ◽

2021 ◽

Vol 11 (5) ◽

Author(s):

Sæmundur Rögnvaldsson ◽

Thorvardur Jon Love ◽

Sigrun Thorsteinsdottir ◽

Elín Ruth Reed ◽

Jón Þórir Óskarsson ◽

...

Keyword(s):

Multiple Myeloma ◽

Early Treatment ◽

Monoclonal Gammopathy ◽

Controlled Trial ◽

Participation Rate ◽

Population Based ◽

Early Therapy ◽

Screening Study ◽

Undetermined Significance

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

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Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients

Blood Cancer Journal ◽

10.1038/s41408-021-00505-4 ◽

2021 ◽

Vol 11 (6) ◽

Author(s):

A. Visram ◽

C. Soof ◽

S. V. Rajkumar ◽

S. K. Kumar ◽

S. Bujarski ◽

...

Keyword(s):

Monoclonal Gammopathy ◽

Serum Samples ◽

Risk Models ◽

Independent Validation ◽

Increased Risk ◽

Risk Of Progression ◽

Paired Serum ◽

Smoldering Myeloma ◽

Undetermined Significance

AbstractSoluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07–5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45–2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.

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Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

Blood Advances ◽

10.1182/bloodadvances.2017007609 ◽

2017 ◽

Vol 1 (24) ◽

pp. 2186-2192 ◽

Cited By ~ 13

Author(s):

Marianna Thordardottir ◽

Ebba K. Lindqvist ◽

Sigrun H. Lund ◽

Rene Costello ◽

Debra Burton ◽

...

Keyword(s):

Body Mass Index ◽

Multiple Myeloma ◽

Body Mass ◽

Monoclonal Gammopathy ◽

High Body Mass Index ◽

Population Based ◽

Population Based Study ◽

Increased Risk ◽

Key Points ◽

Undetermined Significance

Key PointsObesity is not associated with MGUS or LC-MGUS. High body mass index during midlife is associated with increased risk of progressing from MGUS and LC-MGUS to MM and other LP diseases.

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SURVIVAL ADVANTAGE OF APOE2

Innovation in Aging ◽

10.1093/geroni/igz038.2313 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S621-S621

Author(s):

Sudha Seshadri

Keyword(s):

Lower Risk ◽

Large Population ◽

Population Based ◽

European Ancestry ◽

Aggregated Data ◽

Risk Of Death ◽

Apoe Ε4 ◽

Increased Risk ◽

Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

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